The Repertoire of CD4+ CD28− T Cells in Rheumatoid Arthritis

Schmidt, Dorle; Martens, Peter; Weyand, Cornelia M.; Goronzy, Jörg J.

doi:10.1007/bf03401644

Cited by 108 publications

(90 citation statements)

References 38 publications

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“…Studies from various laboratories have consistently demonstrated that these oligoclonal T cells are deficient in expression of the CD28 costimulatory receptor (17,(35)(36)(37). CD4ϩ,CD28 null T cells are long-lived, functionally aberrant lymphocytes (38).…”

Section: Discussionmentioning

confidence: 99%

Modulation of CD28 expression with anti–tumor necrosis factor α therapy in rheumatoid arthritis

Bryl¹,

Vallejo²,

Matteson³

et al. 2005

Arthritis & Rheumatism

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126

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Objective. The immune system of patients with rheumatoid arthritis (RA) is characterized by the accumulation of CD4؉ T cells deficient in CD28 expression and the up-regulation of tumor necrosis factor ␣ (TNF␣). Previous in vitro studies have shown that TNF␣ induces transcriptional silencing of the CD28 gene. Because reduced expression of CD28 in T cells compromises immunocompetence, we examined whether CD28 expression is reduced in patients with RA in vivo and whether the reduction is related to TNF␣.Methods. Patients with RA and age-matched individuals were recruited. Peripheral blood mononuclear cells were stained for CD3, CD4, CD8, CD28, TNF receptor I (TNFRI), and TNFRII, and analyzed by quantitative flow cytometry. The number of CD28 and TNFR molecules was monitored in a subgroup of patients with RA undergoing treatment with anti-TNF␣.Results. In addition to higher frequencies of CD28 null T cells, patients with RA had significantly reduced numbers of CD28 and TNFRI molecules on CD4؉,CD28؉ T cells. Normal expression could be restored in vitro by overnight culture, suggesting that CD28 in patients was modulated by exogenous factors. In contrast, treatment with TNF␣ in vitro resulted in further down-regulation. CD28 expression was normalized in patients undergoing TNF␣-neutralizing therapy.Conclusion. Overproduction of TNF␣ in RA induces a global down-regulation of CD28 in CD4؉ T cells and may cause reduced sensitivity to costimulatory signals in T cell responses.

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Section: Discussionmentioning

confidence: 99%

Modulation of CD28 expression with anti–tumor necrosis factor α therapy in rheumatoid arthritis

Bryl¹,

Vallejo²,

Matteson³

et al. 2005

Arthritis & Rheumatism

Self Cite

126

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show abstract

“…It has been suggested that an unusual subset of CD4 ϩ CD28 null T cells is expanded in RA (47,48). These T cells are likely to require costimulatory signals distinct from CD80/CD86.…”

Section: Costimulation In Ramentioning

confidence: 99%

Interactions of T Cells with Fibroblast-Like Synoviocytes: Role of the B7 Family Costimulatory Ligand B7-H3

Tran

Thacker

Louie

et al. 2008

The Journal of Immunology

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Fibroblast-like synoviocytes (FLS) and T cells can activate each other in vitro, and in vivo interactions between these cells may be important in rheumatoid arthritis (RA), yet FLS lack significant expression of CD28 ligands. We sought to identify molecules homologous to CD28 ligands that are strongly expressed by FLS, and documented strong B7-H3 expression on FLS and by fibroblasts of other tissues, which was unaffected by a variety of cytokines. Western blot analysis of FLS lysates showed predominant expression of the larger, four Ig-like domain isoform of B7-H3. Immunohistological sections of RA synovial tissue showed strong staining for B7-H3 on FLS. Cells expressing B7-H3 were distinct from but in close proximity to cells that expressed CD45, CD20, and CD3. Confocal microscopy of FLS and T cell cocultures showed localization of B7-H3 in the region of the T cell-FLS contact point, but distinct from the localization of T cell CD11a/CD18 (LFA-1) and FLS CD54 (ICAM-1). Reduction of B7-H3 expression on FLS by RNA interference affected interactions of FLS with resting T cells or cytokine-activated T cells. Resting T cells showed increased production of TNF-α, IFN-γ, and IL-2, whereas cytokine-activated T cells showed reduced cytokine production relative to control. However, cytokine production by T cells activated through their TCR was not notably altered by knock down of B7-H3. These observations suggest that B7-H3 may be important for the interactions between FLS and T cells in RA, as well as other diseases, and the outcome of such interactions depends on the activation state of the T cell.

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“…Possibly, CD4ϩ,CD28Ϫ T cells recognize alloantigens on FLS lines. However, CD4ϩ,CD28Ϫ T cells are generally oligoclonal (39) and have been shown to be defective in alloreactive responses (40). In contrast, CD4ϩ,CD28Ϫ T cells respond vigorously in autologous mixed-lymphocyte reactions and may indeed be autoreactive (26).…”

Section: Discussionmentioning

confidence: 99%

Fractalkine mediates T cell–dependent proliferation of synovial fibroblasts in rheumatoid arthritis

Sawai¹,

Park²,

He³

et al. 2007

Arthritis & Rheumatism

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The Repertoire of CD4+ CD28− T Cells in Rheumatoid Arthritis

Cited by 108 publications

References 38 publications

Modulation of CD28 expression with anti–tumor necrosis factor α therapy in rheumatoid arthritis

Modulation of CD28 expression with anti–tumor necrosis factor α therapy in rheumatoid arthritis

Interactions of T Cells with Fibroblast-Like Synoviocytes: Role of the B7 Family Costimulatory Ligand B7-H3

Fractalkine mediates T cell–dependent proliferation of synovial fibroblasts in rheumatoid arthritis

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